The proposed studies are designed to clarify the interaction of various hormones and prostaglandins on the isolated glomerulus of the kidney. Furthermore, they include investigations of the mechanism of cellular action, specifically the cyclic nucleotides, of these hormones in the glomerulus. As a first step, and extended investigation of normal prostglandin synthesis and factors controlling it is planned for the isolated glomerulus. Methods to be employed include specific radioimmunoassays for the various prostaglandins and thin layer radiochromatography using labled arachidonate as precursor for prostaglandins. Next, we plan a correlation of glomerular prostaglandin synthesis with the associated alterations of glomerular function in various models of kidney disease. The second objective is to study the cellular mechanism of various agents, e.g., prostaglandins, parathyroid hormone, vasopressin, catecholamine, calcium, etc., in isolated golmeruli. Studies will include measurements of cyclic AMP, cyclic GMP, cAMP and cGMP phosphodiesterases, cAMP-dependent and independent protein kinases, etc. These studies will then be extended to models of experimental kidney disease. These studies will allow us to better understand the role and mechanism of action of prostaglandins and other agents in controlling glomerular function in normal physiology and under pathophysiological conditions.